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Howe was born in Pittsburgh, Pennsylvania. He is an alumnus of the University of Wyoming, and signed his first playing contract at age 24, with the Pittsburgh Pirates in 1971. He came to the major leagues as a part-time player with Pittsburgh in 1974–75, before a trade to the Astros for infielder Tommy Helms on January 6, 1976. He played all four infield positions, mostly as a third baseman and second baseman, for Houston from 1976–82. In only playing in 125 games in 1977 and alternating between 2B, SS and 3B, Howe only committed 8 errors. On May 7, 1980, Art suffered a fractured jaw when hit by a pitch from Expos pitcher Scott Sanderson. After missing the entire 1983 season with an injury, he finished his playing career with the St. Louis Cardinals (1984–85). The right-handed hitter appeared in 891 games over all or parts of 11 seasons, compiling a lifetime batting average of .260 with 43 home runs.

In 1986, Howe began his coaching career as an aide to Bobby Valentine with the Texas Rangers. After three seasons, he was hired by his old team, the Astros, as manager for 1989, succeeding Hal Lanier. Howe enjoyed a successful first season in Houston, but the team was rebuilding with young players such as Jeff Bagwell and Craig Biggio, and suffered losing years in 1990–91. In 1992 and 1993 the Astros improved to .500 and then a winning record, but Howe was fired in favor of Terry Collins at the close of the '93 campaign. During the 1994–95 Dominican Winter League season, Howe led the Azucareros del Este to their first championship.

After a year as a Major League scout for the Los Angeles Dodgers, and spending 1995 as bench coach for the Colorado Rockies, Howe was selected to replace the high-profile Tony La Russa as manager of the Athletics for 1996. The A's suffered through three losing seasons under Howe before, in 1999, they returned to contention. In 2000, 2001 and 2002, the A's won 91, 102 and 103 games respectively and made the American League playoffs in each season. But they did not win a playoff series, and Howe and general managerBilly Beane grew estranged. At the end of 2002, despite a seven-year mark of 600–533 (.530), Howe was released from his Oakland contract to become the highly paid manager of the New York Mets.

The late Oscar-winning actor Philip Seymour Hoffman portrayed Howe in the film Moneyball, which dramaticized Billy Beane's tactics of using sabermetrics to select players. Howe stated that he was unhappy with his portrayal in both the film and the Michael Lewis book it was based on, in which Howe was portrayed as a stubborn traditionalist who refused to follow Beane's plans and a figurehead who acquiesced while Beane ran the A's from the clubhouse.[1] He said it was unfortunate that Beane's lack of regard for him was that obvious.

Howe in 2014

Howe's two years in New York proved highly unsuccessful. The Mets won only 42 percent of their games, the front office went through three general managers, and attendance at Shea Stadium fell. In September 2004, word of Howe's impending firing was leaked to the media two weeks before the season ended, but he was allowed to finish the year. Ultimately, the general manager of the club, Omar Minaya, replaced Howe with Willie Randolph, bench coach for the New York Yankees.

On October 16, 2006, Howe was hired as the third base coach and an infield instructor by the Philadelphia Phillies. After the Texas Rangers hired Ron Washington – a former coach under Howe in Oakland – as their new manager, the Phillies gave Howe permission to speak with the Rangers about any openings in the organization. On November 7, 2006, Howe was hired by the Rangers as Washington's bench coach. He served two years in that role (2007–08) but his contract was not renewed at the end of the Rangers' disappointing 2008 season.